1pf7: Difference between revisions

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[[Image:1pf7.gif|left|200px]]


{{Structure
==CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H==
|PDB= 1pf7 |SIZE=350|CAPTION= <scene name='initialview01'>1pf7</scene>, resolution 2.60&Aring;
<StructureSection load='1pf7' size='340' side='right'caption='[[1pf7]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
|SITE=
== Structural highlights ==
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=IMH:1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL'>IMH</scene>
<table><tr><td colspan='2'>[[1pf7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PF7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PF7 FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMH:1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL'>IMH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pf7 OCA], [https://pdbe.org/1pf7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pf7 RCSB], [https://www.ebi.ac.uk/pdbsum/1pf7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pf7 ProSAT]</span></td></tr>
 
</table>
'''CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH IMMUCILLIN H'''
== Disease ==
 
[https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:[https://omim.org/entry/613179 613179]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.<ref>PMID:3029074</ref> <ref>PMID:1384322</ref> <ref>PMID:8931706</ref>
 
== Function ==
==Overview==
[https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.<ref>PMID:2104852</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pf/1pf7_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pf7 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6A resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP.
Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6A resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP.


==Disease==
Structural basis for inhibition of human PNP by immucillin-H.,Filgueira de Azevedo W Jr, Canduri F, Marangoni dos Santos D, Pereira JH, Dias MV, Silva RG, Mendes MA, Basso LA, Palma MS, Santos DS Biochem Biophys Res Commun. 2003 Oct 3;309(4):917-22. PMID:13679061<ref>PMID:13679061</ref>
Known diseases associated with this structure: Neutral lipid storage disease with myopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609059 609059]], Nucleoside phosphorylase deficiency, immunodeficiency due to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164050 164050]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1PF7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PF7 OCA].
</div>
<div class="pdbe-citations 1pf7" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis for inhibition of human PNP by immucillin-H., Filgueira de Azevedo W Jr, Canduri F, Marangoni dos Santos D, Pereira JH, Dias MV, Silva RG, Mendes MA, Basso LA, Palma MS, Santos DS, Biochem Biophys Res Commun. 2003 Oct 3;309(4):917-22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/13679061 13679061]
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Purine-nucleoside phosphorylase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Basso LA]]
[[Category: Basso, L A.]]
[[Category: Canduri F]]
[[Category: Canduri, F.]]
[[Category: De Azevedo Jr WF]]
[[Category: Dias, M V.B.]]
[[Category: Dias MVB]]
[[Category: Jr., W F.De Azevedo.]]
[[Category: Dos Santos DM]]
[[Category: Mendes, M A.]]
[[Category: Mendes MA]]
[[Category: Palma, M S.]]
[[Category: Palma MS]]
[[Category: Pereira, J H.]]
[[Category: Pereira JH]]
[[Category: Santos, D M.Dos.]]
[[Category: Santos DS]]
[[Category: Santos, D S.]]
[[Category: Silva RG]]
[[Category: Silva, R G.]]
[[Category: IMH]]
[[Category: SO4]]
[[Category: crystallography]]
[[Category: drug design]]
[[Category: purine nucleoside phosphorylase]]
[[Category: synchrotron]]
 
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